The Sarah W. Stedman Nutrition and Metabolism Center at Duke has developed a research-dedicated Metabolomics core laboratory that conducts metabolic, endocrine, inflammatory marker, and physiologic profiling of cultured cells, as well as tissue and bodily fluid samples from animal models and human subjects. Its role in the current program will be to provide both targeted and non-targeted mass spectrometry (MS)- based metabolic profiling assays in tissue and blood fluid samples for all of the projects. The core will also provide key assays of peptide hormones such as IGF-1, IGF-1 binding proteins, growth hormone, and leptin for Project 1, as well as insulin and glucose measurements to support Project 4. The core will also develop or refine novel metabolomics technologies relevant to this program, including development of new chromatography methods for resolving isobaric metabolites such as leucine and isoleucine in MS assays, targeted assays for distal metabolites in the BCAA and Tyr/Phe catabolic pathways, and refinement of non- targeted GC/MS-based metabolic profiling methods. Participation of this core in the program is highly significant because it provides powerful capabilities for detecting changes in metabolite levels in multiple tissues and bodily fluids in response to genetic and dietary manipulations, thereby providing insights into key mechanisms underlying development of insulin resistance and type 2 diabetes. RELEVANCE (See Instructions): Participation of this core in the program is highly relevant because it provides powerful capabilities for detecting changes in metabolite levels in multiple tissues and bodily fluids in response to genetic and dietary manipulations, thereby providing insights into key mechanisms underlying development of insulin resistance and type 2 diabetes.